Endocrine Abstracts

A 30 year-old man was assessed for gynaecomastia. He had been treated for GH deficiency from the age of 3 to 16. His non-consanguineous parents were of short stature (maternal height 1.22 m, paternal height 1.58 m), as was a half-sister (1.55 m). The patient’s height was 1.55 m with an arm span of 1.48 m and his BMI was 31. Testicular volume was 18 mL and secondary sexual characteristics were normally developed. Lipomastia was diagnosed and subsequently treated surgically.

The karyotype was confirmed as 46, XY. In addition to reduced IGF-1 levels, persistently low prolactin and fT4 concentrations were noted, in the presence of inappropriately ‘normal’ TSH levels (see table). An ITT confirmed GH deficiency and a normal cortisol response. A TRH test was also normal. Baseline FSH was 5.6 IU/l (1–10), LH 3.2 IU/l (1–9) and testosterone 15.7 mmol/l (9–26). Pituitary appearances on MRI were unremarkable. GH therapy was consequently restarted.

These results are suggestive of a mutation in the pituitary-specific transcription factor-1 gene (PIT-1) and genetic tests are currently being performed on this family. A defect in PIT-1 simultaneously impairs somatotroph, lactotroph and thyrotroph cell development. Embryological PIT-1 expression is regulated by the ‘Prophet of PIT-1’ transcription factor (PROP-1), which additionally controls gonadotroph and possibly corticotroph ontogenesis. Inactivating PROP-1 mutations lead to hypogonadism and occur as sporadic cases because the disorder is consequently not transmitted. PIT-1 mutations, however, should be considered in the differential diagnosis of familial cases of combined pituitary hormone deficiency with low GH, PRL and TSH levels.